Acta Chimica Sinica ›› 2005, Vol. 63 ›› Issue (23): 2131-2136. Previous Articles     Next Articles

酪氨酸蛋白磷酸酯酶1B抑制剂的分子对接和三维定量构效关系研究

周梅1, 章威2, 成元华3, 计明娟1, 徐筱杰2   

  1. 1. 中国科学院研究生院化学与化学工程学院, 北京, 100049;
    2. 北京大学化学与分子工程学院, 北京, 100871;
    3. 北京工业大学环境与能源工程学院, 北京, 100022
  • 投稿日期:2005-03-28 修回日期:2005-06-28 发布日期:2014-02-14
  • 通讯作者: 计明娟,E-mail:jmj@gscas.ac.cn;Tel:010-88256326. E-mail:jmj@gscas.ac.cn
  • 基金资助:

    国家自然科学基金(No.20373089);中国科学院研究生院启动基金(No.M3004)资助项目

Molecular Docking and 3D-QSAR Studies on Protein Tyrosine Phosphatase 1B Inhibitors

ZHOU Mei1, ZHANG Wei2, CHENG Yuan-Hua3, JI Ming-Juan1, XU Xiao-Jie2   

  1. 1. College of Chemistry and Chemical Engineering, Graduate University of Chinese Academy of Sciences, Beijing 100049;
    2. College of Chemistry and Molecular Engineering, Peking University, Beijing 100871;
    3. College of Environmental and Energy Engineering, Beijing University of Technology, Beijing 100022
  • Received:2005-03-28 Revised:2005-06-28 Published:2014-02-14

Here a molecular docking and 3D-QSAR study is reported on a series of 2-(oxalic mono-amido)benzoic acid (OBA) inhibitors and protein tyrosine phosphatase 1B (PTP1B). Firstly, a flexible docking method (FlexX) was used to place 12 OBA inhibitors into the active site of PTP1B. The predicted binding affinities of the molecules were found to be linearly relevant to their experimental activities (pKi, non-cross-validated R2=0.859). After that, 33 OBA inhibitors were fixed into the predicted binding con-formation, and were studied using CoMFA method. The resulting CoMFA model (cross-validated q2=0.650) could predict the activity of 6 molecules in the test set within a mean unsigned error of 0.177, and match the characters of our binding mode perfectly. The discovered binding mode could provide hints to further modification of inhibitors.

Key words: protein tyrosine phosphatase, molecular docking, 3D-QSAR, CoMFA